Control design for multicast-aware class-based networks

The expectations of citizens from the Information Technologies (ITs) are increasing as the ITs have become integral part of our society, serving all kinds of activities whether professional, leisure, safety-critical applications or business. Hence, the limitations of the traditional network designs to provide innovative and enhanced services and applications motivated a consensus to integrate all services over packet switching infrastructures, using the Internet Protocol, so as to leverage flexible control and economical benefits in the Next Generation Networks (NGNs). However, the Internet is not capable of treating services differently while each service has its own requirements (e.g., Quality of Service - QoS). Therefore, the need for more evolved forms of communications has driven to radical changes of architectural and layering designs which demand appropriate solutions for service admission and network resources control. This Thesis addresses QoS and network control issues, aiming to improve overall control performance in current and future networks which classify services into classes. The Thesis is divided into three parts. In the first part, we propose two resource over-reservation algorithms, a Class-based bandwidth Over-Reservation (COR) and an Enhanced COR (ECOR). The over-reservation means reserving more bandwidth than a Class of Service (CoS) needs, so the QoS reservation signalling rate is reduced. COR and ECOR allow for dynamically defining over-reservation parameters for CoSs based on network interfaces resource conditions; they aim to reduce QoS signalling and related overhead without incurring CoS starvation or waste of bandwidth. ECOR differs from COR by allowing for optimizing control overhead minimization. Further, we propose a centralized control mechanism called Advanced Centralization Architecture (ACA), that uses a single state-full Control Decision Point (CDP) which maintains a good view of its underlying network topology and the related links resource statistics on real-time basis to control the overall network. It is very important to mention that, in this Thesis, we use multicast trees as the basis for session transport, not only for group communication purposes, but mainly to pin packets of a session mapped to a tree to follow the desired tree. Our simulation results prove a drastic reduction of QoS control signalling and the related overhead without QoS violation or waste of resources. Besides, we provide a generic-purpose analytical model to assess the impact of various parameters (e.g., link capacity, session dynamics, etc.) that generally challenge resource overprovisioning control. In the second part of this Thesis, we propose a decentralization control mechanism called Advanced Class-based resource OverpRovisioning (ACOR), that aims to achieve better scalability than the ACA approach. ACOR enables multiple CDPs, distributed at network edge, to cooperate and exchange appropriate control data (e.g., trees and bandwidth usage information) such that each CDP is able to maintain a good knowledge of the network topology and the related links resource statistics on real-time basis. From scalability perspective, ACOR cooperation is selective, meaning that control information is exchanged dynamically among only the CDPs which are concerned (correlated). Moreover, the synchronization is carried out through our proposed concept of Virtual Over-Provisioned Resource (VOPR), which is a share of over-reservations of each interface to each tree that uses the interface. Thus, each CDP can process several session requests over a tree without requiring synchronization between the correlated CDPs as long as the VOPR of the tree is not exhausted. Analytical and simulation results demonstrate that aggregate over-reservation control in decentralized scenarios keep low signalling without QoS violations or waste of resources. We also introduced a control signalling protocol called ACOR Protocol (ACOR-P) to support the centralization and decentralization designs in this Thesis. Further, we propose an Extended ACOR (E-ACOR) which aggregates the VOPR of all trees that originate at the same CDP, and more session requests can be processed without synchronization when compared with ACOR. In addition, E-ACOR introduces a mechanism to efficiently track network congestion information to prevent unnecessary synchronization during congestion time when VOPRs would exhaust upon every session request. The performance evaluation through analytical and simulation results proves the superiority of E-ACOR in minimizing overall control signalling overhead while keeping all advantages of ACOR, that is, without incurring QoS violations or waste of resources. The last part of this Thesis includes the Survivable ACOR (SACOR) proposal to support stable operations of the QoS and network control mechanisms in case of failures and recoveries (e.g., of links and nodes). The performance results show flexible survivability characterized by fast convergence time and differentiation of traffic re-routing under efficient resource utilization i.e. without wasting bandwidth. In summary, the QoS and architectural control mechanisms proposed in this Thesis provide efficient and scalable support for network control key sub-systems (e.g., QoS and resource control, traffic engineering, multicasting, etc.), and thus allow for optimizing network overall control performance.

Managing sales people strategically when promoting new products: Incorporating market orientation into a sales management control framework

Salespeople play a pivotal role in promoting new products. Therefore, managers need to know what control mechanism (i.e., output-based control, behavior-based control, or knowledge-based control) can improve their salespeople's new product sales performance. Furthermore, managers may be able to assist salespeople in performing better by having a strong market orientation. The literature has been inconsistent regarding the effects of sales management control mechanisms and has not yet incorporated market orientation into a sales management control framework. The current study surveyed 315 Taiwanese salespeople from publicly traded electronics companies with the aim of contributing to the sales management literature. The results show that sales management controls can directly affect salespeople's innovativeness, which, in turn, affects new product sales performance. However, sales management controls cannot affect performance directly. Furthermore, market orientation can positively moderate the relationship between salespeople's innovativeness and new product sales performance.

Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?

Objective Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.Methods We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks.Results All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero.Conclusion The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system. J Hypertens 29: 2454-2461 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Electrocortical indices of cognitive control in working memory : exploring the effects of proactive interference, cognitive load, and aging

Cognitive control involves the ability to flexibly adjust cognitive processing in order to resist interference and promote goal-directed behaviour. Although frontal cortex is considered to be broadly involved in cognitive control, the mechanisms by which frontal brain areas implement control functions are unclear. Furthermore, aging is associated with reductions in the ability to implement control functions and questions remain as to whether unique cortical responses serve a compensatory role in maintaining maximal performance in later years. Described here are three studies in which electrophysiological data were recorded while participants performed modified versions of the standard Sternberg task. The goal was to determine how top-down control is implemented in younger adults and altered in aging. In study I, the effects of frequent stimulus repetition on the interference-related N450 were investigated in a Sternberg task with a small stimulus set (requiring extensive stimulus resampling) and a task with a large stimulus set (requiring no stimulus resampling).The data indicated that constant stimulus res amp ling required by employing small stimulus sets can undercut the effect of proactive interference on the N450. In study 2, younger and older adults were tested in a standard version of the Sternberg task to determine whether the unique frontal positivity, previously shown to predict memory impairment in older adults during a proactive interference task, would be associated with the improved performance when memory recognition could be aided by unambiguous stimulus familiarity. Here, results indicated that the frontal positivity was associated with poorer memory performance, replicating the effect observed in a more cognitively demanding task, and showing that stimulus familiarity does not mediate compensatory cortical activations in older adults. Although the frontal positivity could be interpreted to reflect maladaptive cortical activation, it may also reflect attempts at compensation that fail to fully ameliorate agerelated decline. Furthermore, the frontal positivity may be the result of older adults' reliance on late occurring, controlled processing in contrast to younger adults' ability to identify stimuli at very early stages of processing. In the final study, working memory load was manipulated in the proactive interference Sternberg task in order to investigate whether the N450 reflects simple interference detection, with little need for cognitive resources, or an active conflict resolution mechanism that requires executive resources to implement. Independent component analysis was used to isolate the effect of interference revealing that the canonical N450 was based on two dissociable cognitive control mechanisms: a left frontal negativity that reflects active interference resolution, , but requires executive resources to implement, and a right frontal negativity that reflects global response inhibition that can be relied on when executive resources are minimal but at the cost of a slowed response. Collectively, these studies advance understanding of the factors that influence younger and older adults' ability to satisfy goal-directed behavioural requirements in the face of interference and the effects of age-related cognitive decline.

Role of E3-ligase parkin in mitochondrial quality control in a cardiotoxicity model to anthracyclines

Dues à leur importance croissante dans la dégénérescence musculaire, les mitochondries sont de plus en plus étudiées en relation à diverses myopathies. Leurs mécanismes de contrôle de qualité sont reconnus pour leur rôle important dans la santé mitochondrial. Dans cette étude, nous tentons de déterminer si le déficit de mitophagie chez les souris déficiente du gène Parkin causera une exacerbation des dysfonctions mitochondriales normalement induite par la doxorubicine. Nous avons analysé l’impact de l’ablation de Parkin en réponse à un traitement à la doxorubicine au niveau du fonctionnement cardiaque, des fonctions mitochondriales et de l’enzymologie mitochondriale. Nos résultats démontrent qu’à l’état basal, l’absence de Parkin n’induit pas de pathologie cardiaque mais est associé à des dysfonctions mitochondriales multiples. La doxorubicine induit des dysfonctions respiratoires, du stress oxydant mitochondrial et une susceptibilité à l’ouverture du pore de transition de perméabilité (PTP). Finalement, contrairement à notre hypothèse, l’absence de Parkin n’accentue pas les dysfonctions mitochondriales induites par la doxorubicine et semble même exercer un effet protecteur.

Desarrollo de un estado de la cuestión acerca de las interacciones entre el control de gestión y el aprendizaje organizacional.

Las organizaciones en la actualidad deben encontrar diferentes maneras de sobrevivir en un tiempo de rápida transformación. Uno de los mecanismos usados por las empresas para adaptarse a los cambios organizacionales son los sistemas de control de gestión, que a su vez permiten a las organizaciones hacer un seguimiento a sus procesos, para que la adaptabilidad sea efectiva. Otra variable importante para la adaptación es el aprendizaje organizacional siendo el proceso mediante el cual las organizaciones se adaptan a los cambios del entorno, tanto interno como externo de la compañía. Dado lo anterior, este proyecto se basa en la extracción de documentación soporte valido, que permita explorar las interacciones entre estos dos campos, los sistemas de control de gestión y el aprendizaje organizacional, además, analizar el impacto de estas interacciones en la perdurabilidad organizacional. ​

Reprogramming the cell cycle machinery to treat cardiovascular disease

Coronary artery disease is one of the most common heart pathologies. Restriction of blood flow to the heart by atherosclerotic lesions, leading to angina pectoris and myocardial infarction, damages the heart, resulting in impaired cardiac function. Damaged myocardium is replaced by scar tissue since surviving cardiomyocytes are unable to proliferate to replace lost heart tissue. Although narrowing of the coronary arteries can be treated successfully using coronary revascularisation procedures, re-occlusion of the treated vessels remains a significant clinical problem. Cell cycle control mechanisms are key in both the impaired cardiac repair by surviving cardiomyocytes and re-narrowing of treated vessels by maladaptive proliferation of vascular smooth muscle cells. Strategies targeting the cell cycle machinery in the heart and vasculature offer promise both for the improvement of cardiac repair following MI and the prevention of restenosis and bypass graft failure following revascularisation procedures.

Distributed access control and privacy for the internet of me

This article presents an experimental scalable message driven IoT and its security architecture based on Decentralized Information Flow Control. The system uses a gateway that exports SoA (REST) interfaces to the internet simplifying external applications whereas uses DIFC and asynchronous messaging within the home environment.

Performance evaluation on electronic control systemsfor field sprayers using programmable logic controllers

The aim of this study was to develop a laboratory method for time response evaluation on electronically controlled spray equipment using Programmable Logic Controllers (PLCs). For that purpose, a PLC controlled digital drive inverter was set up to drive an asynchronous electric motor linked to a centrifugal pump on a experimental sprayer equipped with electronic flow control. The PLC was operated via RS232 serial communication from a PC computer. A user program was written to control de motor by adjusting the following system variables, all related to the motor speed: time stopped; ramp up and ramp down times, time running at a given constant speed and ramp down time to stop the motor. This set up was used in conjunction with a data acquisition system to perform laboratory tests with an electronically controlled sprayer. Time response for pressure stabilization was measured while changing the pump speed by +/-20%. The results showed that for a 0.2 s ramp time increasing the motor speed, as an example, an AgLogix Flow Control system (Midwest Technologies Inc.) took 22 s in average to readjust the pressure. When decreasing the motor speed, this time response was down to 8 s. General results also showed that this kind of methodology could make easier the definition of standards for tests on electronically controlled application equipment.

Assessment of aquatic plants in the reservoirs of AES-Tiete and development of an integrated control model for the most important species

The general objective of this work was to develop a monitoring and management model for aquatic plants that could be used in reservoir cascades in Brazil, using the reservoirs of AES-Tiete as a study case. The investigations were carried out at the reservoirs of Barra-Bonita, Bariri, Ibitinga, Promissao, and Nova-Avanhandava, located in the Tiete River Basin; Agua Vermelha, located in the Grande River Basin; Caconde, Limoeiro, and Euclides da Cunha, which are part of the Pardo River Basin; and the Mogi-Guacu reservoir, which belongs to the Mogi-Guacu River basin. The main products of this work were: development of techniques using satellite-generated images for monitoring and planning aquatic plant control; planning and construction of a boat to move floating plant masses and an airboat equipped with a DGPS navigation and application flow control system. Results allowed to conclude that the occurrence of all types of aquatic plants is directly associated with sedimentation process and, consequently, with nutrient and light availability. Reservoirs placed at the beginning of cascades are more subject to sedimentation and occurrence of marginal, floating and emerged plants, and are the priority when it comes to controlling these plants, since they provide a supply of weeds for the other reservoirs. Reservoirs placed downstream show smaller amounts of water-suspended solids, with greater transmission of light and occurrence of submerged plants.

Critical parameter determination of sonic flow controller diamond microtubes and micronozzles

In this article, the authors measure throughput of sonic diamond microtubes and micronozzles that can work as passive gas flow controllers and flow meters under choking conditions. The behavior of the outlet pressure through the microdevices using an experimental setup with constant volume and constant temperature was determined in order to obtain the critical throughput, the critical mass flow rate, and the discharge coefficients of the diamond sonic microdevices. © 2007 American Vacuum Society.

Suppression of vortex-induced vibration using moving surface boundary-layer control

Experimental results of flow around a circular cylinder with moving surface boundary-layer control (MSBC) are presented. Two small rotating cylinders strategically located inject momentum in the boundary layer of the cylinder, which delays the separation of the boundary layer. As a consequence, the wake becomes narrower and the fluctuating transverse velocity is reduced, resulting in a recirculation free region that prevents the vortex formation. The control parameter is the ratio between the tangential velocity of the moving surface and the flow velocity (U-c/U). The main advantage of the MSBC is the possibility of combining the suppression of vortex-induced vibration (VIV) and drag reduction. The experimental tests are preformed at a circulating water channel facility and the circular cylinders are mounted on a low-damping air bearing base with one degree-of-freedom in the transverse direction of the channel flow. The mass ratio is 1.8. The Reynolds number ranges from 1600 to 7500, the reduced velocity varies up to 17, and the control parameter interval is U-c/U = 5-10. A significant decreasing in the maximum amplitude of oscillation for the cylinder with MSBC is observed. Drag measurements are obtained for statically mounted cylinders with and without MSBC. The use of the flow control results in a mean drag reduction at U-c/U = 5 of almost 60% compared to the plain cylinder. PIV velocity fields of the wake of static cylinders are measured at Re = 3000. The results show that the wake is highly organized and narrower compared to the one observed in cylinders without control. The calculation of the total variance of the fluctuating transverse velocity in the wake region allows the introduction of an active closed-loop control. The experimental results are in good agreement with the numerical simulation studies conducted by other researchers for cylinders with MSBC. (C) 2012 Elsevier Ltd. All rights reserved.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Reliable Broadcasting and Streaming of Multimedia Content

This thesis is focused on the study of techniques that allow to have reliable transmission of multimedia content in streaming and broadcasting applications, targeting in particular video content. The design of efficient error-control mechanisms, to enhance video transmission systems reliability, has been addressed considering cross-layer and multi-layer/multi-dimensional channel coding techniques to cope with bit errors as well as packet erasures. Mechanisms for unequal time interleaving have been designed as a viable solution to reduce the impact of errors and erasures by acting on the time diversity of the data flow, thus enhancing robustness against correlated channel impairments. In order to account for the nature of the factors which affect the physical layer channel in the evaluation of FEC schemes performances, an ad-hoc error-event modeling has been devised. In addition, the impact of error correction/protection techniques on the quality perceived by the consumers of video services applications and techniques for objective/subjective quality evaluation have been studied. The applicability and value of the proposed techniques have been tested by considering practical constraints and requirements of real system implementations.

Control of protein degradation pathways by BAG proteins and changes during aging

Many age-related neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and polyglutamine disorders, including Huntington’s disease, are associated with the aberrant formation of protein aggregates. These protein aggregates and/or their precursors are believed to be causally linked to the pathogenesis of such protein conformation disorders, also referred to as proteinopathies. The accumulation of protein aggregates, frequently under conditions of an age-related increase in oxidative stress, implies the failure of protein quality control and the resulting proteome instability as an upstream event of proteinopathies. As aging is a main risk factor of many proteinopathies, potential alterations of protein quality control pathways that accompany the biological aging process could be a crucial factor for the onset of these disorders.rnrnThe focus of this dissertation lies on age-related alterations of protein quality control mechanisms that are regulated by the co-chaperones of the BAG (Bcl-2-associated athanogene) family. BAG proteins are thought to promote nucleotide exchange on Hsc/Hsp70 and to couple the release of chaperone-bound substrates to distinct down-stream cellular processes. The present study demonstrates that BAG1 and BAG3 are reciprocally regulated during aging leading to an increased BAG3 to BAG1 ratio in cellular models of replicative senescence as well as in neurons of the aging rodent brain. Furthermore, BAG1 and BAG3 were identified as key regulators of protein degradation pathways. BAG1 was found to be essential for effective degradation of polyubiquitinated proteins by the ubiquitin/proteasome system, possibly by promoting Hsc/Hsp70 substrate transfer to the 26S proteasome. In contrast, BAG3 was identified to stimulate the turnover of polyubiquitinated proteins by macroautophagy, a catabolic process mediated by lysosomal hydrolases. BAG3-regulated protein degradation was found to depend on the function of the ubiquitin-receptor protein SQSTM1 which is known to sequester polyubiquitinated proteins for macroautophagic degradation. It could be further demonstrated that SQSTM1 expression is tightly coupled to BAG3 expression and that BAG3 can physically interact with SQSTM1. Moreover, immunofluorescence-based microscopic analyses revealed that BAG3 co-localizes with SQSTM1 in protein sequestration structures suggesting a direct role of BAG3 in substrate delivery to SQSTM1 for macroautophagic degradation. Consistent with these findings, the age-related switch from BAG1 to BAG3 was found to determine that aged cells use the macroautophagic system more intensely for the turnover of polyubiquitinated proteins, in particular of insoluble, aggregated quality control substrates. Finally, in vivo expression analysis of macroautophagy markers in young and old mice as well as analysis of the lysosomal enzymatic activity strongly indicated that the macroautophagy pathway is also recruited in the nervous system during the organismal aging process.rnrnTogether these findings suggest that protein turnover by macroautophagy is gaining importance during the aging process as insoluble quality control substrates are increasingly produced that cannot be degraded by the proteasomal system. For this reason, a switch from the proteasome regulator BAG1 to the macroautophagy stimulator BAG3 occurs during cell aging. Hence, it can be concluded that the BAG3-mediated recruitment of the macroauto-phagy pathway is an important adaptation of the protein quality control system to maintain protein homeostasis in the presence of an enhanced pro-oxidant and aggregation-prone milieu characteristic of aging. Future studies will explore whether an impairment of this adaptation process may contribute to age-related proteinopathies.